This application is to support a program that will consolidate and coordinate five groups whose research focuses on Drosophila. The research areas include: gene structure and regulation, developmental genetics, neurogenetics, analysis of transposable elements, and population and evolutionary genetics. The groups are united by common application of similar genetic and molecular methodologies. Specific projects are: (1A) The possibility that the heat shock protein, hsp 70, represses its own transcription will be analyzed by fusing the coding region with the promoter of a constitutively expressed heat shock cognate gene and assaying in vivo expression of this hybrid gene following transformation. (1B) The functional role of heat shock and related proteins will be studied by mutational analysis of a gene encoding a heat shock cognate expressed abundantly and constitutively during normal development. (2) The structure and function of ion channels in excitable membranes will be studied by molecular and genetic analysis of the para locus and genes encoding the acetylcholine receptor (AChR). The para locus will be cloned via P element-induced mutant alleles. AChR clones will be recovered using heterologous DNA probes or antibody screening of cDNA expression libraries and the chromosomal sites of origin of these clones mutated. (3) The effects of P elements on other transposable elements and on neighboring genes will be investigated by monitoring the mobilization of known transposable elements under dysgenic conditions in a general survey and by molecular characterization of a particular set of unstable alleles that lack P in inserts but respond to P element transposase. A set of P insertions into the sn locus will also be characterized with respect to phenotype, site of insertion and structure of inserted element. (4) The function of the decapentaplegic (dpp) gene complex which is involved in normal embryonic and adult pattern formation will be studied by assaying segments of the complex for ability to rescue specific dpp phenotypes following reintroduction via transformation. Functional units of the gene complex will be further defined at the molecular level by in vitro deletion analysis to determine the minimal functional fragments. (5) The basis for the lower than expected frequency of segregation distorter (SD) chromosomes in nature despite their non-Mendelian advantage in transmission will be examined by testing SD males for reduced fitness caused by sperm competition in multiple matings. We will explore a novel method of using P elements to provide a differential molecular tag of different classes of sperm. Performance of these projects will be expedited and strengthened by drawing on complementary areas of expertise of the project members. Results of these studies will provide new information about the genetic and molecular mechanisms of gene expression, development, behavior and evolution of Drosophila with obvious implications for human biology as well.